The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing

Hum Mol Genet. 2010 Apr 1;19(7):1153-64. doi: 10.1093/hmg/ddp585. Epub 2010 Jan 6.

Abstract

The loss of HBII-52 and related C/D box small nucleolar RNA (snoRNA) expression units have been implicated as a cause for the Prader-Willi syndrome (PWS). We recently found that the C/D box snoRNA HBII-52 changes the alternative splicing of the serotonin receptor 2C pre-mRNA, which is different from the traditional C/D box snoRNA function in non-mRNA methylation. Using bioinformatic predictions and experimental verification, we identified five pre-mRNAs (DPM2, TAF1, RALGPS1, PBRM1 and CRHR1) containing alternative exons that are regulated by MBII-52, the mouse homolog of HBII-52. Analysis of a single member of the MBII-52 cluster of snoRNAs by RNase protection and northern blot analysis shows that the MBII-52 expressing unit generates shorter RNAs that originate from the full-length MBII-52 snoRNA through additional processing steps. These novel RNAs associate with hnRNPs and not with proteins associated with canonical C/D box snoRNAs. Our data indicate that not a traditional C/D box snoRNA MBII-52, but a processed version lacking the snoRNA stem is the predominant MBII-52 RNA missing in PWS. This processed snoRNA functions in alternative splice-site selection. Its substitution could be a therapeutic principle for PWS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Animals
  • Gene Expression Regulation
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism
  • Mice
  • Prader-Willi Syndrome / genetics*
  • RNA Editing
  • RNA Precursors
  • RNA, Small Nucleolar*
  • Receptor, Serotonin, 5-HT2C / genetics*

Substances

  • Heterogeneous-Nuclear Ribonucleoproteins
  • RNA Precursors
  • RNA, Small Nucleolar
  • Receptor, Serotonin, 5-HT2C